We appreciate the thoughtful comments by Dr. Gupta et al. regarding our systematic review. Their commitment to this rare but emerging clinical topic is welcome, and we would like to address the methodological points rais...We appreciate the thoughtful comments by Dr. Gupta et al. regarding our systematic review. Their commitment to this rare but emerging clinical topic is welcome, and we would like to address the methodological points raised.
BACKGROUND: Despite advances in digital health, many interventions fail, not due to technical shortcomings, but because they are not meaningfully adopted or sustained in everyday life. Understanding real-world engagement...BACKGROUND: Despite advances in digital health, many interventions fail, not due to technical shortcomings, but because they are not meaningfully adopted or sustained in everyday life. Understanding real-world engagement remains a critical gap, especially in under-explored domains such as olfactory health. This study aimed to evaluate the real-world feasibility of a home-based Digital Smell Training (DST) system, focusing on how - participants - engage with it and sustain its use over time. METHODOLOGY: A six-month real-world feasibility study of a DST system, combining a scent-delivery device and mobile app, was tested in 18 UK households with and without olfactory disorders. A mixed methods approach captured adherence and user experiences over time. RESULTS: Participants completed 74% of 5,600 potential sessions, showing high adherence to twice-daily training. Qualitative data revealed dynamic behavioural patterns: users’ motivations fluctuated over time, shaped by perceived progress, novelty effects, and evolving relationships with the intervention. CONCLUSIONS: This study offers rare insight into how people engage with unfamiliar digital health tools outside controlled settings. Beyond the specific use case of smell, our findings highlight design and engagement strategies essential for achieving real-world impact, showing that sustained adoption hinges not just on innovation, but on behavioural understanding.
The international opinion paper by Whitcroft et al. provides invaluable guidance for the emerging field of olfactory implants (1). While the authors thoroughly address clinical considerations and current technological ap...The international opinion paper by Whitcroft et al. provides invaluable guidance for the emerging field of olfactory implants (1). While the authors thoroughly address clinical considerations and current technological approaches, we would like to expand upon Statements 9.1 and 9.3 regarding electrode technology limitations and highlight recent advances in brain-computer interface (BCI) technology that could address key technological challenges around electrode longevity and biocompatibility.
Caminati M, Mastrototaro A, Maule M
… +11 more, Schiappoli M, Vaia R, Zurlo M, Bini F, Brussino L, Dâ Amato M, Marra AM, Nicola S, Schroeder JWV, Senna G, Benoni R
BACKGROUD: The efficacy of tezepelumab in chronic rhinosinusitis with nasal polyps (CRSwNP) has been demonstrated in clinical trials, but real-world evidence remains limited. Our study investigated the trend of CRSwNP ou...BACKGROUD: The efficacy of tezepelumab in chronic rhinosinusitis with nasal polyps (CRSwNP) has been demonstrated in clinical trials, but real-world evidence remains limited. Our study investigated the trend of CRSwNP outcomes in patients prescribed with tezepelumab for severe asthma and the impact of upper airways comorbidity on asthma outcomes over a 6 months follow-up. METHODS: Data from 5 referral centres for severe asthma and CRSwNP were retrospectively analysed. Patient reported outcomes and objective measures related to nasal (SNOT-22, VAS, nasal polyp score) and bronchial (asthma control test, lung function) evaluation were assessed at baseline, 3 and 6 months after tezepelumab initiation. RESULTS: Tezepelumab significantly and rapidly improved all the nasal outcomes and asthma-related parameters, irrespective of sex, body mass index, prior biologic use, or disease duration. Furthermore, significant reduction of oral corticosteroid use, hospitalizations and exacerbations were also observed. When comparing patients with and without CRSwNP, no differences were observed in term of treatment response. CONCLUSIONS: In patients with severe asthma and CRSwNP, tezepelumab demonstrated to induce in the real-life setting an overall rapid and sustained improvement of nasal outcomes, as well as of lung function and clinical parameters in asthma patients regardless of upper airway involvement. Although larger studies are needed, these findings contribute to the positioning of tezepelumab in the real-world clinical practice according to a precision medicine approach.
Lazzeroni M, Hoven R, de Corso E
… +10 more, Montuori C, Sedaghat AR, Sarafidou A, Constantinidis J, Hopkins C, Castro BR, Patel Z, Capaccio P, Fokkens WJ, Reitsma S
BACKGROUND: Despite optimal medical and surgical therapy, many patients suffering from chronic rhinosinusitis (CRS) experience continuous inflammation for which revision surgery can be indicated. The present work was set...BACKGROUND: Despite optimal medical and surgical therapy, many patients suffering from chronic rhinosinusitis (CRS) experience continuous inflammation for which revision surgery can be indicated. The present work was set out to investigate the extent of prior endoscopic sinus surgery (ESS) performed in CRS patients referred to tertiary rhinologic centers for revision surgery in Western countries. METHODS: A retrospective multicenter study was conducted including patients with any (pheno)type of diffuse CRS, who had undergone at least one prior ESS. All patients had a sinus computed tomography (CT) scan performed before their revision surgery which was used to retrieve the Amsterdam classification of completeness of ESS (ACCESS) scores, which range from 0 (sinuses functionally opened) to 24 (no sinus opening). RESULTS: 114 patients from 6 different centers were included. The median ACCESS score was 12 (7-17). Most patients had only one previous ESS (70/114, 61%), while 24 (21%) had 2 previous surgeries, 13 (11.4%) patients had three, and 7 (6%) patients had four or more. Median ACCESS scores by number of previous ESS were: 13 (6-16) for one prior surgery, 12 (7-18) for two, 10 (8-13) for three, and 6 (3-13) for four or more surgeries. Multivariate linear regression analysis showed small changes in the patient’s ACCESS score in relation to their number of previous surgeries. CONCLUSIONS: Our study underscores a large heterogeneity in extent of prior ESS among patients referred to tertiary rhinologic centers for diffuse CRS, regardless of the number of previous surgeries.
The COVID-19 pandemic brought attention to post-viral smell distortion, or parosmia, which is defined as a qualitative dysfunction resulting from distorted odor perception in the presence of an odorous medium (1). Very o...The COVID-19 pandemic brought attention to post-viral smell distortion, or parosmia, which is defined as a qualitative dysfunction resulting from distorted odor perception in the presence of an odorous medium (1). Very often, qualitative and quantitative alterations occur simultaneously. Patients severely affected by qualitative odor disorders find that their quality of life has deteriorated (2). For quantitative loss from viruses, the role of olfactory training has been emphasized (3), along with high volume steroid nasal irrigations (4), and even injections with platelet-rich plasma (5). However, there has been no high-level evidence demonstrating an effective treatment for qualitative olfactory disorders.
Patients with chronic rhinosinusitis (CRS) commonly have ear complaints (ECs). Reported prevalences in CRS-patients vary up to 61%, and even higher (82%) in patients with nasal polyps (CRSwNP) with an indication for surg...Patients with chronic rhinosinusitis (CRS) commonly have ear complaints (ECs). Reported prevalences in CRS-patients vary up to 61%, and even higher (82%) in patients with nasal polyps (CRSwNP) with an indication for surgery. These data, however, are not based on validated otologic surveys. Instead, the ear-related questions of the SinoNasal Outcome Test 22-items (SNOT-22) (5) are used. ECs are often overlooked as CRSwNP patients present primarily with nasal complaints, despite the impact on quality of life of this co-morbidity. With the advent of biological therapy for severe uncontrolled CRSwNP, comorbidities are increasingly appreciated including the rare but debilitating eosinophilic otitis media (EOM). This study investigates ECs, evaluated by otologic questionnaires, in a severe uncontrolled CRSwNP population. It also investigates the use of single SNOT-22 ear items as proxy for relevant ECs.
BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak is a significant complication of endoscopic skull base surgery (ESBS) that increases meningitis risk, a serious and potentially life-threatening infection. This st...BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak is a significant complication of endoscopic skull base surgery (ESBS) that increases meningitis risk, a serious and potentially life-threatening infection. This study aimed to delineate the risk factors associated with the development of meningitis in patients who experienced postoperative CSF leakage. METHODOLOGY: We reviewed 1,303 ESBS cases for skull base lesion between January 2020 and July 2024 at a single tertiary center. Patient demographics, pathology, intraoperative CSF leak grade, reconstruction techniques, and postoperative CSF leak management strategiesâ€"including the use of nasoseptal flaps, fat grafts, and lumbar drainsâ€"were collected. Clinical and surgical factors were analyzed among patients with postoperative CSF leak to identify associations with the development of meningitis. RESULTS: Postoperative CSF leak was suspected in 49 patients (3.8%). Among them, 36 (2.8%) underwent repair surgery, while 13 (1.0%) were treated conservatively without surgical confirmation. Meningitis occurred in 21 of these patients. Multivariate analysis revealed that intraoperative CSF leak grade, use of fat grafts, lumbar drain insertion, and delayed CSF leak recognition were significantly associated with meningitis development. Patients with grade 3 intraoperative leaks had 3.21-fold increased odds of developing meningitis compared to grade 0. Tumor pathology, nasoseptal flap viability, and hydroxyapatite use were not significantly associated. CONCLUSIONS: The transition from postoperative CSF leak to meningitis is influenced by the severity of intraoperative leakage, reconstructive choices, and the timing of leak detection. Restricting fat grafts and lumbar drains to selected cases and ensuring close postoperative rhinologic surveillance are critical in mitigating infectious complications following ESBS.
INTRODUCTION: Recurrent anterior idiopathic epistaxis is common in children, yet optimal management remains debated. This study compared the efficacy of antiseptic cream, antiseptic plus corticosteroid cream, and silver...INTRODUCTION: Recurrent anterior idiopathic epistaxis is common in children, yet optimal management remains debated. This study compared the efficacy of antiseptic cream, antiseptic plus corticosteroid cream, and silver nitrate cautery in reducing epistaxis severity in paediatric patients. METHODOLOGY: In a prospective randomised dual-centre clinical trial, 136 children with recurrent idiopathic anterior epistaxis were evenly allocated to antiseptic cream, antiseptic plus corticosteroid cream, or silver nitrate cautery. Epistaxis Severity Score was assessed at baseline, 2 weeks, and 1, 3, and 6 months. RESULTS: All groups showed significant reductions in ESS over time. At 2 weeks, silver nitrate cautery produced the most rapid early improvement, compared with antiseptic cream and the combination cream. By 1 month, the antiseptic plus corticosteroid group showed the greatest improvement, with further reductions at 3 months and 6 months. At 6 months, improvement rates were highest with the combination therapy, followed by antiseptic cream and cautery. CONCLUSIONS: Cautery achieves rapid short-term control, but antiseptic plus corticosteroid cream provides the most durable improvement following a short, two-week course. It should be considered a first-line therapy for recurrent idiopathic anterior epistaxis in children.
The nasal and paranasal cavities constitute integral components of the vocal tract resonator system, yet their precise contribution to voice quality remains a subject of debate. While early anatomical and acoustic models...The nasal and paranasal cavities constitute integral components of the vocal tract resonator system, yet their precise contribution to voice quality remains a subject of debate. While early anatomical and acoustic models (1-3) suggested that sinus coupling through open ostia may introduce anti-resonances and spectral alterations, subsequent investigations employing cadaveric dissections, physical simulations, and three-dimensional replicas (4, 5) have confirmed notable effects on frequency response and formant balance. Clinical studies, including those examining patients with chronic rhinosinusitis undergoing functional endoscopic sinus surgery (FESS), have shown that surgical management can improve both sinonasal and vocal quality of life without adverse effects on voice characteristics (6,7). However, conventional acoustic measures such as jitter and shimmer frequently fail to detect such changes (8). In contrast, Mel-frequency cepstral coefficients (MFCCs), which transform the speech spectrum into a perceptually weighted domain, have shown superior sensitivity to resonance-related shifts and hypernasality (9). Based on this evidence, we investigated whether MFCCs and spectral flatness can more accurately identify post-operative alterations in resonance that are not captured by traditional acoustic parameters.
Biologic therapies targeting type 2 inflammation, such as dupilumab, omalizumab, and mepolizumab, have been developed to manage chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in patients with comorbid as...Biologic therapies targeting type 2 inflammation, such as dupilumab, omalizumab, and mepolizumab, have been developed to manage chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in patients with comorbid asthma or aspirin-exacerbated respiratory disease (AERD). Functional endoscopic sinus surgery (FESS) remains the mainstay of treatment in patients who are refractory to medical therapy. However, direct comparisons between biologic therapy and FESS are limited. This systematic review and meta-analysis aimed to compare sinonasal outcomes between FESS and biologic therapy in real-world settings.
Several population-based studies have reported increased prevalence of autoimmune diseases (AID) in patients with chronic rhinosinusitis (CRS). Large-scale datasets from Taiwan demonstrated associations between CRS and c...Several population-based studies have reported increased prevalence of autoimmune diseases (AID) in patients with chronic rhinosinusitis (CRS). Large-scale datasets from Taiwan demonstrated associations between CRS and conditions such as rheumatoid arthritis, ankylosing spondylitis, polymyositis, psoriasis, Sjogren's syndrome, and systemic lupus erythematosus (SLE). However, sex-specific patterns have not been investigated.
Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a significant burden on the healthcare system. Xian et al. discussed several aspects of our economic model, based on French pricing, that may impact the cost-e...Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a significant burden on the healthcare system. Xian et al. discussed several aspects of our economic model, based on French pricing, that may impact the cost-effectiveness of biologics . Briefly, they outlined the regional disparities in the cost of biologics, the potential better outcomes of biologics in real-world evidence, and the recurrence rate after endoscopic sinus surgery (ESS). We think that these aspects may be further discussed.
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory condition often classified into eosinophilic (Eos) and non-eosinophilic (nonEos) subtypes. While microbial dysbiosis and metab...BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory condition often classified into eosinophilic (Eos) and non-eosinophilic (nonEos) subtypes. While microbial dysbiosis and metabolic disturbance are known contributors to CRSwNP, the interplay between sinonasal microbiota and local metabolic activity remains unclear. METHODS: We conducted 16S rRNA gene sequencing and untargeted metabolomics on sinonasal swabs and tissue samples from patients with Eos-CRSwNP (n = 14), nonEos CRSwNP (n = 7), and healthy controls (n = 14). Microbial diversity, taxonomic differences, and metabolic alterations were analyzed. Spearman correlation and network modeling were used to explore phenotype-specific microbiotaâ€"metabolite interactions and pathway enrichment. RESULTS: Eos CRSwNP was characterized by reduced microbial diversity and increased abundance of Staphylococcus and Corynebacterium, along with elevated levels of fumaric acid, linoleic acid, and arachidonic acidâ€"metabolites linked to oxidative stress and lipid-mediated inflammation. In contrast, nonEos-CRSwNP exhibited greater microbial richness, with enrichment of Streptococcus, Anaerococcus, and Clostridium XlVa, and metabolic shifts in amino acid and nitrogen metabolism, including increased glutamine, taurine, and ethanolamine phosphate. Correlation analysis revealed phenotype-specific networks connecting core microbial genera and metabolites, suggesting distinct inflammatory microenvironments between subtypes. CONCLUSION: Our integrated multi-omics analysis highlights divergent microbial and metabolic signatures in Eos and nonEos CRSwNP. These findings offer mechanistic insights into subtype-specific disease processes and may guide the future development of targeted diagnostic and therapeutic strategies.
We read with keen interest the article by Kawabata et al. titled "Olfactory disorder after COVID-19 vaccination" which explores 16 cases of olfactory dysfunction temporally associated with vaccination. The paper addresse...We read with keen interest the article by Kawabata et al. titled "Olfactory disorder after COVID-19 vaccination" which explores 16 cases of olfactory dysfunction temporally associated with vaccination. The paper addresses an important and under-recognized topic; however, several methodological aspects warrant clarification to aid accurate interpretation. First, the inclusion of five institutional cases within a review otherwise presented as PRISMA-compliant raises questions regarding methodological consistency. Under PRISMA, all included studies should be identified through transparent and reproducible database searches. Clarifying whether institutional data were processed separately from literature-derived cases would strengthen transparency and avoid confusion about the evidence level.
BACKGROUND: The impact of endoscopic sinus surgery (ESS) extent on long-term disease control and therapeutic escalation in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to evaluate th...BACKGROUND: The impact of endoscopic sinus surgery (ESS) extent on long-term disease control and therapeutic escalation in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to evaluate the clinical applicability of endoscopy-based criteria for therapeutic escalation and to determine the impact of surgical extent on the risk and timing of treatment intensification. METHODS: A retrospective cohort study with 3-year follow-up was conducted. CRSwNP patients who underwent ESS were included and classified according to Lamella Ostium Extent Mucosa (LOEM) system (t1â€"t4). Baseline characteristics and disease severity measures were assessed. Therapeutic escalation was defined by endoscopic criteria. Predictors of escalation and the effect of ESS extent on escalation timing across clinical phenotypes were analyzed using multivariate logistic regression, Kaplan-Meier curves and Cox regressions. RESULTS: In the overall sample (n=172), patients who required escalation showed higher SNOT-22 scores and poorer olfactory function. More extensive ESS (LOEM t3â€"t4) was associated with significantly reduced escalation risk and prolonged disease control. Post hoc analyses confirmed significant pairwise differences favoring extensive (t3â€"t4) over limited (t1â€"t2) surgery. Subgroup analyses demonstrated greater benefits in older subjects, atopic patients, revision surgeries and patients with eosinophils >300cells/μL. Higher baseline SNOT-22 scores remained an independent predictor of escalation after ESS. CONCLUSIONS: Surgical extent appears to influence both escalation risk and timing. More extensive ESS may provide more sustained control, particularly in revision cases and biomarker-defined subgroups, supporting its integration into personalized algorithms.
BACKGROUND: Emerging evidence has highlighted a potential link between chronic rhinosinusitis with nasal polyps (CRSwNP) and coronavirus disease 2019 (COVID-19). However, the exact mechanism driving this association is n...BACKGROUND: Emerging evidence has highlighted a potential link between chronic rhinosinusitis with nasal polyps (CRSwNP) and coronavirus disease 2019 (COVID-19). However, the exact mechanism driving this association is not well understood. We aimed to explore the biological pathways and differentially expressed genes (DEGs) involved in CRSwNP and COVID-19 by performing bioinformatic analyses. METHODS: Data from the GEO database was analyzed using the "limma" package to identify DEGs. Techniques like weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks, and machine learning were employed to pinpoint key genes. Single-sample gene set enrichment analysis (ssGSEA) was used to assess immune cell infiltration. Key gene expression in macrophages was verified using single-cell analysis and immunofluorescence. Genetranscription factor-microRNA (gene-TF-miRNA) regulatory networks were constructed via NetworkAnalyst. Potential therapeutic agents were identified through DGIdb. Nasal polyps and control nasal tissues were surgically obtained for validation purposes. RESULTS: The findings revealed 19 co-DEGs common to both CRSwNP and COVID-19, which were enriched in pathways related to inflammation and the immune response. Among these genes, CD163 was identified as the key gene. The infiltration of CD163+ macrophages was substantially greater in the nasal tissues of CRSwNP and COVID-19 patients than in those of control subjects. Fluticasone was determined to be a promising drug that targets CD163. CONCLUSION: This study highlights CD163 as a promising diagnostic marker for CRSwNP and COVID-19, suggesting that targeting CD163 may be pivotal in the management of these conditions.
Topical corticosteroids are standard therapy in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma, administered as nasal corticosteroids (NCS) and inhaled corticosteroid (ICS). Suboptimal adherence is associat...Topical corticosteroids are standard therapy in chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma, administered as nasal corticosteroids (NCS) and inhaled corticosteroid (ICS). Suboptimal adherence is associated with impaired health-related quality of life.
BACKGROUND: Biologic therapy has emerged as a key treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in refractory cases, but its effect on healthcare utilization is not well established. METHO...BACKGROUND: Biologic therapy has emerged as a key treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in refractory cases, but its effect on healthcare utilization is not well established. METHODOLOGY: We conducted a retrospective big-data analysis using the Clalit Health Services database, identifying all CRSwNP patients treated with dupilumab or mepolizumab following endoscopic sinus surgery (ESS) between 2010â€"2024. We assessed antibiotic and systemic steroid use, visits to clinics, emergency rooms (ER), hospitalizations, and repeat ESS before and after biologic initiation. RESULTS: Among 861 patients (54.2% on dupilumab, 45.8% on mepolizumab), 62% had asthma. Median therapy duration was 25 months. Mean follow-up was 130 ± 78 months before treatment and 43 ± 42 months after. Biologics significantly reduced antibiotic and systemic steroid use, as well as community clinic, hospitalization, and revision ESS rates. Serum eosinophils declined from 520 ± 440 to 430 ± 460 cells/μL. CONCLUSIONS: Post-ESS biologic therapy in CRSwNP patients is associated with reduced healthcare utilization and systemic medication use, highlighting its positive impact on disease burden and healthcare efficiency.
BACKGROUND: There is often a discrepancy between official recommendations and actual clinical practice on repair of congenital choanal atresia (CA). The objective of this study was to evaluate the current state of care f...BACKGROUND: There is often a discrepancy between official recommendations and actual clinical practice on repair of congenital choanal atresia (CA). The objective of this study was to evaluate the current state of care for CA patients in Germany. METHODS: An online survey was conducted in which 108 German ENT departments were consulted on various aspects of CA management, including preoperative diagnosis, surgical procedures, and postoperative care. RESULTS: 65% of the ENT departments only perform CA repairs at over 3 years of age. Flexible nasal endoscopy (69%), hearing tests (41%), and computed tomography (52%) were preoperative diagnosis tools. Posterior vomer was resected in 56% of the ENT departments. Scar- (60%), granulation tissue (38%), and insufficient vomer resections (21%) caused recurrences. Stents were used by 38%. CONCLUSIONS: Elective unilateral CA repair should be performed in time to minimise symptoms. Preoperative hearing tests should be introduced as routine to identify CA patients with hearing problems. The utilisation of preoperative computed tomography should be discussed individually. Only just over half of the participating ENT departments resected posterior vomer parts. This is a significant starting point with the potential to improve the recurrence rates of this patient cohort. Stent use is still quite common iin Germany. This should be changed in the future.